Helicobacter pylori modulation of gastric and duodenal mucosal T cell cytokine secretions in children compared with adults.

BACKGROUND: In contrast to adults, ulcers are un-common in Helicobacter pylori-infected children. Since immunological determinants influence the outcome of H. pylori infection, we have investigated mucosal T cell responses in H. pylori-infected children and compared them with those of adults and negative controls. MATERIAL AND METHODS: Mucosal biopsies were obtained from 43 patients undergoing an upper GI endoscopy for dyspeptic symptoms. The concentrations of released cytokines and the density of CD3+, CD25+ and CD69+cells were evaluated by flow cytometry, and the numbers of cytokine-secreting cells were measured by ELISPOT. RESULTS: The numbers of isolated antral CD3+ lymphocytes were only significantly raised in infected adults compared with noninfected controls (p < 0.05), whereas the proportion of CD3+ cells expressing activation markers (CD25 or CD69) remained low. In the stomach, IFN-gamma concentrations increased in infected children and infected adults compared with controls (p < 0.05), but IFN-gamma concentrations were tenfold lower in children than in adults (p < 0.01). IL-2, IL-4, IL-10 and TNF-alpha concentrations were similar in infected and in uninfected children and adults. In contrast, in the duodenum, IFN-gamma, as well as IL-4 and IL-10 concentrations were only increased in infected children compared with controls (p < 0.05). The concentrations of these cytokines were similar in both groups of adults who, however, like children, displayed a higher number of duodenal IL-4-secreting cells compared to controls (p < 0.05). CONCLUSION: These results suggest that IFN-gamma secretion in the stomach of H. pylori-infected patients is lower in children than in adults. This could protect children from development of severe gastro-duodenal diseases such as ulcer disease. In addition, infected patients are characterised by a dysregulation of the mucosal cytokine secretion at distance from the infection site.

BMP signaling in the development of the mouse esophagus and forestomach.

The stratification and differentiation of the epidermis are known to involve the precise control of multiple signaling pathways. By contrast, little is known about the development of the mouse esophagus and forestomach, which are composed of a stratified squamous epithelium. Based on prior work in the skin, we hypothesized that bone morphogenetic protein (BMP) signaling is a central player. To test this hypothesis, we first used a BMP reporter mouse line harboring a BRE-lacZ allele, along with in situ hybridization to localize transcripts for BMP signaling components, including various antagonists. We then exploited a Shh-Cre allele that drives recombination in the embryonic foregut epithelium to generate gain- or loss-of-function models for the Bmpr1a (Alk3) receptor. In gain-of-function (Shh-Cre;Rosa26(CAG-loxpstoploxp-caBmprIa)) embryos, high levels of ectopic BMP signaling stall the transition from simple columnar to multilayered undifferentiated epithelium in the esophagus and forestomach. In loss-of-function experiments, conditional deletion of the BMP receptor in Shh-Cre;Bmpr1a(flox/flox) embryos allows the formation of a multilayered squamous epithelium but this fails to differentiate, as shown by the absence of expression of the suprabasal markers loricrin and involucrin. Together, these findings suggest multiple roles for BMP signaling in the developing esophagus and forestomach.

Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133 modify susceptibility to and survival of gastric cancer.

CD133 is one of the most common stem cell markers, and functional single nucleotide polymorphisms (SNPs) of CD133 may modulate its gene functions and thus cancer risk and patient survival. We hypothesized that potentially functional CD133 SNPs are associated with gastric cancer (GC) risk and survival. To test this hypothesis, we conducted a case-control study of 371 GC patients and 313 cancer-free controls frequency-matched by age, sex, and ethnicity. We genotyped four selected, potentially functional CD133 SNPs (rs2240688A>C, rs7686732C>G, rs10022537T>A, and rs3130C>T) and used logistic regression analysis for associations of these SNPs with GC risk and Cox hazards regression analysis for survival. We found that compared with the miRNA binding site rs2240688 AA genotype, AC + CC genotypes were associated with significantly increased GC risk (adjusted OR = 1.52, 95% CI = 1.09-2.13); for another miRNA binding site rs3130C>T SNP, the TT genotype was associated with significantly reduced GC risk (adjusted OR = 0.68, 95% CI = 0.48-0.97), compared with CC + CT genotypes. In all patients, the risk rs3130 TT variant genotype was significantly associated with overall survival (OS) (adjusted P(trend) = 0.016 and 0.007 under additive and recessive models, respectively). These findings suggest that these two CD133 miRNA binding site variants, rs2240688 and rs3130, may be potential biomarkers for genetic susceptibility to GC and possible predictors for survival in GC patients but require further validation by larger studies.

Ptolemaic Mummy Stuffings, 2: A Comic Fragment and Grammatical Text in the Yale Collection (P. CtYBR inv. 5019, 5043)

This is the second installment of a three-part project to publish a group of ten Ptolemaic papyri purchased by Yale’s Beinecke Library in 1998 (acquisition “1998b”), which came to the Beinecke as three hard wads that were apparently the stuffing from the stomach cavity of a mummified animal. This article publishes: (1) P.CtYBR inv. 5019, a fragment of line ends in iambic tetrameter catalectic meter from an unknown comedy; the format suggests that this is a further example of certain type of Ptolemaic writing exercise. (2) P.CtYBR inv. 5043, a fragmentary grammatical text of uncertain import.

Epidemiological study of oesophageal and gastric cancer in south-east England

Background: This epidemiological study was carried out to establish the magnitude of the changing incidence of gastric and oesophageal cancer. Methods: Time-trend analyses of subsite-specific cancers of the oesophagus and stomach were performed using data from the Thames Cancer Registry database (1960-1996) for the South Thames Region. The changes in sex ratio and peak age of incidence are reported. Results: In the upper two-thirds of the oesophagus there was no significant change in the incidence rate, but the lower third of the oesophagus showed a marked rise for both sexes (average annual change + 0.05 for men, + 0.009 for women). For the gastric cardia, the incidence in males increased (average annual change + 0.025), while in females it remained unchanged. Cancers of the oesophagogastric junction showed a clear increase for both sexes (average annual change + 0.07 for men, + 0.009 for women). There were changes in the sex ratio and peak age of incidence for all subsite cancers for both sexes. Conclusion: Over a 37-year period the incidence of cancer of the oesophagogastric junction increased threefold, while the incidence of cancers of the other subsites of the stomach decreased. Further studies are needed to investigate the aetiology of these changes.

Coordinated Rhythms Of Digestion Absorption And Excretion In Mytilus-Edulis (Bivalvia Mollusca)

Sequential alternation of extracellular digestion in the stomach and intracellular digestion in the diverticula appears widespread among bivalves. The present study documents some physiological consequences of such processes in Mytilus edulis L. collected during 1981 from Whitsand Bay, Cornwall, England. Pronounced temporal fluctuations in faecal deposition are described that relate, in terms of amplitude and period, to both sinusoidal rhythmicity established for ammonia excretion and changes in the morphology of digestive tubules. Although at least partially synchronised among replicate groups of mussels, these cycles bore no consistent relationship with exogenous influences. Hourly fluctuation in the net absorption efficiency for nitrogen, as evidenced by the mean percentage ±2 SE, measured over 24 h sampling periods, was considerable (16.0±53.7, 49.3±10.9 and 52.8±6.6 for mussels acclimated in March, June and October, respectively). This variation in absorption derived from an inverse relationship between the percentage nitrogen within faeces and the rate of faecal egestion. Accordingly, peaks of faecal deposition presumably represented the pulsed remnants of intracellular digestion. Co-ordinated rhythms of digestion, absorption and excretion were thus evident in M. edulis. These processes displayed seasonally dependent periodicities of approximately 8, 3 and 4 h in March, June and October, respectively. It was concluded that, at least for M. edulis, this previously unquantified rhythmicity of physiological processes warrants careful consideration during assays commonly undertaken in the complication of nutrient and energy budgets.

Can the Continuous Plankton Recorder (CPR) be used to infer sardine diet?

Knowledge on the impact of climate variability in the diet of planktivorous fish is limited by the laborious work involved in stomach content analysis, impractical for large scale studies. Routine measurements of plankton such as the Continuous Plankton Recorder (CPR) survey provide valuable information of the temporal variation of phyto- and zooplankton prey availability for higher trophic levels. Sardines are a world-wide distributed and commercially important planktivorous fish, at the basis of the pelagic marine food web. Being predominantly non-selective filter-feeders, their diets closely correspond to the water plankton species and a significant relationship was recently found between Sardina pilchardus feeding intensity and remotely sensed chlorophyll alpha . Data of sardine stomach prey composition and CPR were obtained during 2003 for the same location off the west coast of Portugal, an area characterised by strong seasonality of plankton abundance and composition, mainly governed by upwelling events. Phyto- and zooplankton prey in sardine stomachs were identified to the lowest possible taxa and their numerical and volumetric abundance was registered, as well as their contribution to the prey carbon content. The seasonal variation of the abundance and composition of sardine diet was then compared to the abundance and composition of the water plankton obtained with the CPR at the same time and for the same area where the fish were collected, in order to evaluate if CPR data can be used to proxy sardine prey availability and diet composition at large temporal scales.

A synthesis of large-scale patterns in the planktonic prey of larval and juvenile cod (Gadus morhua)

Data from 40 published studies of the diet composition of larval and juvenile cod (Gadus morhua) from around the northern North Atlantic were summarized to assess generic patterns in ontogenetic and regional variability in the key prey. The results showed that larvae at the northern edge of the latitudinal range of cod depend primarily on development stages of the copepod Calanus finmarchicus, whilst those at the southern edge depend on Para- and Pseudocalanus species. Juvenile cod preyed on a wider range of taxa than larvae, but euphausiids were the main target prey. Analysis of regional variations in the relative abundances of C. finmarchicus and Para/Pseudocalanus spp. in the plankton, as estimated by the continuous plankton recorder (CPR) surveys, showed a similar geographical pattern to the larval cod stomach contents. Comparison of CPR data from the 1960s and 70s with data from the 1990s showed that the boundary between C. finmarchicus and Para/Pseudocalanus spp. dominance has shifted northwards on both sides of the Atlantic, whilst the abundance of euphausiids in the southern cod stock regions has declined. The results are discussed in relation to regional differences in the response of cod stocks to climate variability.

Ecological Relations Between the Herring and the Plankton off The North-East Coast of England

I. 430 plankton samples, which were taken by several herring drifters using the Continuous Plankton Recorder in the Shields fishing area during the summer seasons of 1931 to 1933, are analysed to show the main changes in the plankton during those seasons. 2. A comparison is made between the proportions of the different zooplankton organisms found in the plankton and the proportions of these recorded by Savage (1937) in the stomachs of herring obtained from drifters working in the same area and during the same time. The comparisons are made for 29 ten-day periods in the seasons 1931 to 1933, and in addition, for 6 ten-day periods relating to a single drifter which obtained both plankton and stomach samples at the same time in 1932. 3. The comparisons in 2 provide evidence that the herring feeds by selecting certain organisms by individual acts of capture and not by swimming open-mouthed to strain out the plankton indiscriminately: (a) Calanus and Temora in the stomachs either correspond fairly closely to the proportions in the plankton or they may be in very much higher proportions. The latter is always true regarding Anomalocera. (b) Acartia, Oithona, Cladocera and Lamellibranch larvae are always in larger proportions in the plankton than in the stomachs; this applies also to Centropages with two insignificant exceptions. (c) There is a close correspondence between the numbers of Limacina and Sagitta in the plankton and stomachs in the latter half of the 1931 season, but not during 1932 and 1933, when the numbers in the stomachs were insignificant ; during the former period there was a great scarcity of Calanus in the plankton.

Bacterial symbiosis in Syssitomya pourtalesiana Oliver, 2012 (Galeommatoidea: Montacutidae), a bivalve commensal with the deep-sea echinoid Pourtalesia.

For the first time, bacterial symbiosis is recognized in the bivalve family Montacutidae of the superfamily Galeommatoidea. The ctenidial filaments of Syssitomya pourtalesiana Oliver, 2012 are extended abfrontally and a dense layer of bacteriocyte cells cover the entire surface behind a narrow ciliated frontal zone. The bacteria are extracellular and held within a matrix of epithelial extensions and microvilli. There is no cuticular layer (glycocalyx) covering the bacteria as in many thyasirid symbioses. The bacteriocytes hold more than one morphotype of bacteria, but bacilli, 1–3 μm in length, dominate. Scanning electron microscopy observations show a surface mat of filamentous bacteria over the extreme abfrontal surfaces. Filter feeding was confirmed by the presence of food particles in the stomach and the bivalve is presumed to be mixotrophic. Syssitomya is commensal and lives attached to the anal spines of the deep-sea echinoid Pourtalesia. In this position, echinoid feeding currents and echinoid faecal material may supply the bacteria with a variety of nutrient materials including dissolved organic matter.

Upregulation of Oxidative Stress Markers in Human Microvascular Endothelial Cells by Complexes of Serum Albumin and Digestion Products of Glycated Casein

The extent of absorption of dietary advanced glycation end products (AGEs) is not fully known. The possible physiological impact of these absorbed components on inflammatory processes has been studied little and was the aim of this investigation. Aqueous solutions of bovine casein and glucose were heated at 95 degrees C for 5 h to give AGE-casein (AGE-Cas). Simulated stomach and small intestine digestion of AGE-Cas and dialysis (molecular mass cutoff of membrane = 1 kDa) resulted in a low molecular mass (LMM) fraction of digestion products, which was used to prepare bovine serum albumin (BSA)-LMM-AGE-Cas complexes. Stimulation of human microvascular endothelial cells with BSA-LMM-AGE-Cas complexes significantly increased mRNA expression of the receptor of AGE (RAGE), galectin-3 (AGE-113), tumor necrosis factor alpha, and a marker of the mitogen-activated protein kinase pathway (MAPK-1), as well as p65NF-kappa B activation. Cells treated with LMM digestion products of AGE-Cas significantly increased AGE-R3 mRNA expression. Intracellular reactive oxygen species production increased significantly in cells challenged with BSA-LMM-AGE-Cas and LMM-AGE-Cas. In conclusion, in an in vitro cell system, digested dietary AGEs complexed with serum albumin play a role in the regulation of RAGE and down-stream inflammatory pathways. AGE-R3 may protect against these effects.

Phenotype-environment correlations in a putative whitefish adaptive radiation

1. The adaptive radiation of fishes into benthic (littoral) and pelagic (lentic) morphs in post-glaciallakes has become an important model system for speciation. Although these systems are well stud-ied, there is little evidence of the existence of morphs that have diverged to utilize resources in theremaining principal lake habitat, the profundal zone.
2. Here, we tested phenotype-environment correlations of three whitefish (Coregonus lavaretus)morphs that have radiated into littoral, pelagic and profundal niches in northern Scandinavianlakes. We hypothesized that morphs in such trimorphic systems would have a morphology adaptedto one of the principal lake habitats (littoral, pelagic or profundal niches). Most whitefish popula-tions in the study area are formed by a single (monomorphic) whitefish morph, and we furtherhypothesized that these populations should display intermediate morphotypes and niche utiliza-tion. We used a combination of traditional (stomach content, habitat use, gill raker counts) andmore recently developed (stable isotopes, geometric morphometrics) techniques to evaluate pheno-type-environment correlations in two lakes with trimorphic and two lakes with monomorphicwhitefish.
3. Distinct phenotype-environment correlations were evident for each principal niche in whitefishmorphs inhabiting trimorphic lakes. Monomorphic whitefish exploited multiple habitats, hadintermediate morphology, displayed increased variance in gillraker-counts, and relied significantlyon zooplankton, most likely due to relaxed resource competition.
4. We suggest that the ecological processes acting in the trimorphic lakes are similar to each other,and are driving the adaptive evolution of whitefish morphs, possibly leading to the formation ofnew species.

Rapid sympatric ecological differentiation of crater lake cichlid fishes within historic times

Background: After a volcano erupts, a lake may form in the cooled crater and become an isolated aquatic ecosystem. This makes fishes in crater lakes informative for understanding sympatric evolution and ecological diversification in barren environments. From a geological and limnological perspective, such research offers insight about the process of crater lake ecosystem establishment and speciation. In the present study we use genetic and coalescence approaches to infer the colonization history of Midas cichlid fishes (Amphilophus cf. citrinellus) that inhabit a very young crater lake in Nicaragua-the ca. 1800 year-old Lake Apoyeque. This lake holds two sympatric, endemic morphs of Midas cichlid: one with large, hypertrophied lips (~20% of the total population) and another with thin lips. Here we test the associated ecological, morphological and genetic diversification of these two morphs and their potential to represent incipient speciation.
Results: Gene coalescence analyses [11 microsatellite loci and mitochondrial DNA (mtDNA) sequences] suggest that crater lake Apoyeque was colonized in a single event from the large neighbouring great lake Managua only about 100 years ago. This founding in historic times is also reflected in the extremely low nuclear and mitochondrial genetic diversity in Apoyeque. We found that sympatric adult thin- and thick-lipped fishes occupy distinct ecological trophic niches. Diet, body shape, head width, pharyngeal jaw size and shape and stable isotope values all differ significantly between the two lip-morphs. The eco-morphological features pharyngeal jaw shape, body shape, stomach contents and stable isotopes (d15N) all show a bimodal distribution of traits, which is compatible with the expectations of an initial stage of ecological speciation under disruptive selection. Genetic differentiation between the thin- and thick-lipped population is weak at mtDNA sequence (FST = 0.018) and absent at nuclear microsatellite loci (FST < 0.001).
Conclusions: This study provides empirical evidence of eco-morphological differentiation occurring very quickly after the colonization of a new and vacant habitat. Exceptionally low levels of neutral genetic diversity and inference from coalescence indicates that the Midas cichlid population in Apoyeque is much younger (ca. 100 years or generations old) than the crater itself (ca. 1 800 years old). This suggests either that the crater remained empty for many hundreds of years after its formation or that remnant volcanic activity prevented the establishment of a stable fish population during the early life of the crater lake. Based on our findings of eco-morphological variation in the Apoyeque Midas cichlids, and known patterns of adaptation in Midas cichlids in general, we suggest that this population may be in a very early stage of speciation (incipient species), promoted by disruptive selection and ecological diversification.

Metabolic and structural properties of human obestatin {1-23} and two fragment peptides

Obestatin is a peptide produced in the oxyntic mucosa of the stomach and co-localizes with ghrelin on the periphery of pancreatic islets. Several studies demonstrate that obestatin reduces food and water intake, decreases body weight gain, inhibits gastrointestinal motility, and modulates glucose-induced insulin secretion. In this study we evaluated the acute metabolic effects of human obestatin {1-23} and fragment peptides {1-10} or {11-23} in high-fat fed mice, and then investigated their solution structure by NMR spectroscopy and molecular modelling. Obestatins {1-23} and {11-23} significantly reduced food intake (86% and 90% respectively) and lowered glucose responses to feeding, whilst leaving insulin responses unchanged. No metabolic changes could be detected following the administration of obestatin (1-10). In aqueous solution none of the obestatin peptides possessed secondary structural features. However, in a 2,2,2-trifluoroethanol (TFE-d(3))-H2O solvent mixture, the structure of obestatin {1-23} was characterized by an a-helix followed by a single turn helix conformation between residues Pro(4) and Gln(15) and His(19) and Ala(22) respectively. Obestatin {1-10} showed no structural components whereas {11-23} contained an a-helix between residues Val(14) and Ser(20) in a mixed solvent. These studies are the first to elucidate the structure of human obestatin and provide clear evidence that the observed a-helical structures are critical for in vivo activity. Future structure/function studies may facilitate the design of novel therapeutic agents based on the obestatin peptide structure. (C) 2010 Elsevier Inc. All rights reserved.

Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia

Hereditary non-polyposis colorectal cancer (HNPCC), predominantly due to germline MLH1/MSH2 mutations, is the commonest form of hereditary colorectal cancer (CRC), but data in Asians are sparse. We sequenced the MLH1/MSH2 coding and promoter core regions in CRC patients diagnosed below age 40, and/or with multiple primary cancers or familial cancer clustering suggestive of HNPCC, and correlated deleterious mutations with clinical and tumour features. Forty-six Chinese, Malay and Indian kindreds participated. Of the 153 cancers reported in the 46 kindreds, stomach (14%) and urogenital cancers (13%) were the most common extracolonic cancers, whereas endometrial cancer comprised only 7%. Eleven different MLH1 and 12 MSH2 mutations were identified, including nine novel and four recurring mutations in the Chinese. One Indian was a compound heterozygote for an MLH1 and MSH2 mutation. The MLH1/MSH2 mutation data in the Malays and the Indians represents the first in these ethnic groups. Factors strongly associated with deleterious mutations were the Amsterdam criteria, family history of stomach or multiple primary cancers, and MSI-high tumours, whereas family history of endometrial cancer and young cancer age alone correlated poorly. Distinct clinical and molecular characteristics were identified among Asian HNPCC kindreds and may have important clinical implications.